Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Glaxo Operations UK Limited, 980 Great West Road,Brentford,TW8 9GS Trading as: GlaxoSmithKline UK, Stockley Park West, Uxbridge, Middlesex UB11 1BT
Hypersensitivity to cefuroxime or to any of the excipients listed in section 6.1.
Patients with known hypersensitivity to cephalosporin antibiotics.
History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).
As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. In case of severe hypersensitivity reactions, treatment with cefuroxime must be discontinued immediately and adequate emergency measures must be initiated.
Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to cefuroxime, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if cefuroxime is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.
Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as furosemide or aminoglycosides. Renal impairment has been reported during use of these combinations. Renal function should be monitored in the elderly and those with known pre-existing renal impairment (see section 4.2).
Use of cefuroxime may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of other non-susceptible microorganisms (e.g. enterococci and Clostridium difficile), which may require interruption of treatment (see section 4.8).
Antibacterial agent–associated pseudomembranous colitis has been reported with use of cefuroxime and may range in severity from mild to life threatening. This diagnosis should be considered in patients with diarrhoea during or subsequent to the administration of cefuroxime (see section 4.8). Discontinuation of therapy with cefuroxime and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
Zinacef is not formulated for intracameral use. Individual cases and clusters of serious ocular adverse reactions have been reported following unapproved intracameral use of cefuroxime sodium compounded from vials approved for intravenous/intramuscular administration. These reactions included macular oedema, retinal oedema, retinal detachment, retinal toxicity, visual impairment, visual acuity reduced, vision blurred, corneal opacity and corneal oedema.
Due to its spectrum of activity, cefuroxime is not suitable for the treatment of infections caused by Gram-negative non-fermenting bacteria (see section 5.1).
The development of a positive Coombs Test associated with the use of cefuroxime may interfere with cross matching of blood (see section 4.8).
Slight interference with copper reduction methods (Benedict’s, Fehling’s, Clinitest) may be observed. However, this should not lead to false-positive results, as may be experienced with some other cephalosporins.
As a false negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving cefuroxime sodium.
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.
This medicinal product contains 42 mg sodium per vial, equivalent to 2.1% of the WHO recommended maximum daly intake of 2 g sodium for an adult.
This medicinal product contains 83 mg sodium per vial, equivalent to 4.15% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Cefuroxime may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
Cefuroxime is excreted by glomerular filtration and tubular secretion. Concomitant use of probenecid is not recommended. Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level.
High-dosage treatments with cephalosporins should be carried out with caution on patients who are taking strong-acting diuretics (such as furosemide) or potential nephrotoxic preparations (such as aminoglycoside antibiotics), since impairment of renal function through such combinations cannot be ruled out.
Determination of blood/plasma glucose levels: refer to section 4.4.
Concomitant use with oral anticoagulants may give rise to increased international normalised ratio (INR).
There are limited amounts of data from the use of cefuroxime in pregnant women. Studies in animals have shown no reproductive toxicity (see section 5.3). Zinacef should be prescribed to pregnant women only if the benefit outweighs the risk.
Cefuroxime has been shown to cross the placenta and attain therapeutic levels in amniotic fluid and cord blood after intramuscular or intravenous dose to the mother.
Cefuroxime is excreted in human milk in small quantities. Adverse reactions at therapeutic doses are not expected, although a risk of diarrhoea and fungus infection of the mucous membranes cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from cefuroxime therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
There are no data on the effects of cefuroxime sodium on fertility in humans. Reproductive studies in animals have shown no effects on fertility.
No studies on the effects of cefuroxime on the ability to drive and use machines have been performed. However, based on known adverse reactions, cefuroxime is unlikely to have an effect on the ability to drive and use machines.
The most common adverse reactions are neutropenia, eosinophilia, transient rise in liver enzymes or bilirubin, particularly in patients with pre-existing liver disease, but there is no evidence of harm to the liver and injection site reactions.
The frequency categories assigned to the adverse reactions below are estimates, as for most reactions suitable data for calculating incidence are not available. In addition the incidence of adverse reactions associated with cefuroxime sodium may vary according to the indication.
Data from clinical trials were used to determine the frequency of very common to rare adverse reactions. The frequencies assigned to all other adverse reactions (i.e. those occurring at <1/10,000) were mainly determined using post-marketing data, and refer to a reporting rate rather than a true frequency.
Treatment related adverse reactions, all grades, are listed below by MedDRA body system organ class, frequency and grade of severity. The following convention has been utilised for the classification of frequency: very common ≥1/10; common ≥1/100 to <1/10; uncommon ≥1/1,000 to <1/100; rare ≥1/10,000 to <1/1,000; very rare <1/10,000 and not known (cannot be estimated from the available data).
Not known: Candida overgrowth, overgrowth of Clostridium difficile
Common: neutropenia, eosinophilia, decreased haemoglobin concentration
Uncommon: leukopenia, positive Coombs test
Not known: thrombocytopenia, haemolytic anaemia
Not known: drug fever, interstitial nephritis, anaphylaxis, cutaneous vasculitis
Uncommon: gastrointestinal disturbance
Not known: pseudomembranous colitis (see section 4.4)
Common: transient rise in liver enzymes
Uncommon: transient rise in bilirubin
Uncommon: skin rash, urticaria and pruritus
Not known: erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson syndrome, angioneurotic oedema
Not known: elevations in serum creatinine, elevations in blood urea nitrogen and decreased creatinine clearance (see section 4.4)
Common: injection site reactions which may include pain and thrombophlebitis
Cephalosporins as a class tend to be absorbed onto the surface of red cell membranes and react with antibodies directed against the drug to produce a positive Coombs test (which can interfere with cross matching of blood) and very rarely haemolytic anaemia.
Transient rises in serum liver enzymes or bilirubin have been observed which are usually reversible.
Pain at the intramuscular injection site is more likely at higher doses. However it is unlikely to be a cause for discontinuation of treatment.
The safety profile for cefuroxime sodium in children is consistent with the profile in adults.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or by searching for MHRA Yellow Card in the Google Play or Apple App Store.
Cefuroxime is compatible with most commonly used intravenous fluids and electrolyte solutions.
The pH of 2.74% w/v sodium bicarbonate injection BP considerably affects the colour of solutions and therefore this solution is not recommended for the dilution of Zinacef. However, if required, for patients receiving sodium bicarbonate injection by infusion the Zinacef may be introduced into the tube of the giving set.
Zinacef should not be mixed in the syringe with aminoglycoside antibiotics.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
